97 articles - From Friday Sep 09 2022 to Friday Sep 16 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
meta-analyses and systematic reviews
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Clinical Significance of Clonal Hematopoiesis in the Setting of Autologous Stem Cell Transplantation for Lymphoma. In terms of specific gene mutations, adverse OS was mostly associated with PPM1D mutations (hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.13-2.67, P=0.011). In summary, we found that CH is associated with an increased risk of non-lymphoma-related death after ASCT, which suggests that lymphoma survivors with CH may need intensified surveillance strategies to prevent and treat late complications. |
Differential Prognostic Impact of RUNX1 Mutations According to Frontline Therapy in Patients with Acute Myeloid Leukemia. A multivariate analysis showed possible interaction between RUNX1 mutation status and treatment, suggesting a differential prognostic impact of RUNX1 mutations when patients received IC versus LIT with VEN. In summary, the prognostic impact of mRUNX1 AML may be treatment-dependent, and the presence of RUNX1 mutations may not impact clinical outcomes when venetoclax-based regimens are used. |
Erythroferrone contributes to iron mobilization for embryo erythropoiesis in iron-deficient mouse pregnancies. The effect was exacerbated under iron-deficient conditions where ERFE KO embryos had higher hepcidin, lower Hb and Hct, and lower brain iron concentration compared to WT embryos, indicative of iron restriction. Thus, under iron-deficient conditions, maternal and embryo ERFE facilitate iron mobilization for embryonic erythropoiesis. |
Time-dependent prediction of mortality and cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation using machine learning. These gradient boosting machine models provide well-calibrated, time-dependent risk predictions and achieved areas under the receiver-operating characteristic of 0.92 and 0.83 and areas under the precision-recall curve of 0.58 and 0.62 for prediction of mortality and CMV reactivation, respectively, in a 21-day time window. Both models were successfully validated in a prospective, non-interventional study and performed on par with expert hematologists in a pilot comparison. |
Transferrin receptor 2 (Tfr2) genetic deletion makes transfusion-independent a murine model of transfusion-dependent ß-thalassemia. Remarkably, BM Tfr2 deletion is also sufficient to avoid long-term blood transfusions required for survival of Hbb th1/th2 animals, preventing mortality due to chronic anemia and reducing transfusion-associated complications, such as progressive iron-loading. Altogether, TFR2 targeting might represent a promising therapeutic option also for TDT. |
Understanding pulse oximetry in hematology patients: Hemoglobinopathies, racial differences and beyond. In addition, a range of challenges may arise in patients with increased levels of methemoglobin - whether acquired or inherited - carboxyhemoglobin, or in patients with a subset of inherited variant hemoglobins. It is important for Hematologists, and indeed al clinicians who rely on pulse oximetry, to understand the principles and limitations of this ubiquitous test. |
| Ann Oncol |
APOBEC mutagenesis, kataegis, chromothripsis in EGFR-mutant osimertinib-resistant lung adenocarcinomas. APOBEC mutational signatures are frequent in RTK-driven LUADs and increase under the selective pressure of osimertinib in EGFR-mutant lung cancer. APOBEC mutational signature enrichment in subclonal mutations, private mutations acquired after osimertinib treatment, and areas of large scale genomic rearrangements highlights a potentially fundamental role for APOBEC mutagenesis in the development of resistance to targeted therapies, which may be potentially exploited to overcome such resistance. |
The Clinical Landscape of Cell-Free DNA Alterations in 1,671 Patients with Advanced Biliary Tract Cancer. These findings from the largest and most comprehensive study to date of cfDNA from patients with advanced BTC highlight the utility of cfDNA analysis in current management of this disease. Characterization of oncogenic drivers and mechanisms of therapeutic resistance in this study will inform drug development efforts to reduce mortality for patients with BTC. |
| Blood |
Dabrafenib plus trametinib in patients with relapsed/refractory BRAF V600E mutation-positive hairy cell leukemia. Dabrafenib plus trametinib demonstrated durable responses with a manageable safety profile consistent with previous observations in other indications and should be considered as a rituximab-free therapeutic option for patients with relapsed/refractory BRAF V600E mutation-positive HCL. This trial is registered at as #NCT02034110. |
Detecting measurable residual disease beyond 10-4 through an IGHV leader-based NGS approach improves prognostic stratification in CLL. PFS of patients in this MRD range was significantly shorter, compared to patients with MRD <10-5 (HR 4.0, [95%CI 1.6-10.3], P=0.004), but significantly longer, compared to patients with MRD =10-4 (HR 0.44, [95%CI 0.23-0.87], P=0.018). These results support the clinical utility of the IGHV leader-based NGS assay. |
Effective treatment of low risk acute GVHD with itacitinib monotherapy. There were no significant differences between groups at 1-year for non-relapse mortality (4% vs 11%, p=0.21), relapse (18% vs 21%, p=0.64), chronic GVHD (28% vs 33%, p=0.33) or survival (88% vs 80%, p=0.11). Itacitinib monotherapy seems to be a safe and effective alternative to SCS treatment for LR GVHD that deserves further investigation. |
Efficacy and safety of cilta-cel in patients with progressive MM after exposure to other BCMA-targeting agents. Seven (35%) patients died (3 of progressive disease, 4 of adverse events [1 treatment-related, 3 unrelated]). Cilta-cel induced favorable responses in patients with relapsed/refractory MM and prior exposure to anti-BCMA treatment who have exhausted other therapies. |
EVI1 drives leukemogenesis through aberrant ERG activation. Suppression of ERG induces terminal differentiation of EVI1-driven AML cells, whereas ectopic expression of ERG abrogates their dependence on EVI1, indicating that major oncogenic functions of EVI1 are mediated through aberrant transcriptional activation of ERG. Interfering with this regulatory axis may provide entry points for the development of rational targeted therapies. |
Macrophage- and BCR- but not TLR-derived signals support the growth of CLL and Richter Syndrome murine models in vivo. Finally, we show that genetic disruption of IRAK4 does not result in negative selection of human CLL cell lines xenografted in immunodeficient mice. The obtained data suggest that TLR-signals are unlikely to represent a major driver of CLL/RS cell proliferation and provide further evidence that signals from macrophages and the BCR promote the growth and survival of CLL and RS cells in vivo. |
Recombinant Erwinia Asparaginase (JZP458) in Acute Lymphoblastic Leukemia: Results from the Phase 2/3 AALL1931 Study. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 86/167 (51%) patients; TRAEs leading to discontinuation included pancreatitis (6%), allergic reactions (5%), increased alanine aminotransferase (1%), and hyperammonemia (1%). Study results demonstrate that IM JZP458 at 25/25/50 mg/m2 MWF is efficacious and has a safety profile consistent with those of other asparaginases. |
T Overall, Tgd patients displayed reduced survival with respect to Tab patients (p=0.0017). Although there was no difference in STAT3 mutation frequency, our results showed that Tgd LGLL represents a subset of T-LGLL characterized by more frequent symptoms and reduced survival as compared to Tab LGLL. |
The end of the beginning: Application of single cell sequencing to chronic lymphocytic leukemia (CLL). Herein, we review the recent forays into the application of single cell analysis to CLL, which are already revealing new understanding of the natural progression of CLL, the impact of novel therapies, and the interactions with co-evolving non-malignant immune cell populations. As we emerge from the 'end of the beginning' of this technologic revolution, CLL stands poised to reap the benefits of single cell analysis from the standpoints of uncovering fresh fundamental biology, and of providing a path to devising regimes of personalized diagnosis, treatment, and monitoring. |
Trafficking between clonally related peripheral T helper cells and tissue-resident T helper cells in chronic GVHD. Deficiency of IL-21R, BCL6, or T-bet in donor T cells markedly reduced the proportions of Tph cells in the blood and Trh cells in GVHD target tissues and reduced T-B interaction in the lymphoid aggregates. These results indicate that clonally related pathogenic Tph cells and Trh cells traffic between the blood and chronic GVHD target tissues, and that IL-21R-BCL6 signaling and T-bet are required for the development and expansion of Tph and Trh cells in the pathogenesis of cGVHD. |
von Willebrand Factor-binding aptamer rondoraptivon pegol as treatment for severe and non-severe hemophilia A. Rondoraptivon pegol is a first-in-class pro-hemostatic molecule that extended ~3-fold the half-life of substituted FVIII and increased ~2-fold endogenous FVIII levels in hemophilia patients. (NCT04677803). |
| Blood Adv |
Clinical response to belumosudil in bronchiolitis obliterans syndrome: a combined analysis from 2 prospective trials. In conclusion, belumosudil treatment was associated with lung-specific clinical responses for subjects with BOS, which were more commonly observed in less advanced disease. Optimization of treatment response evaluations remains a challenge in patients with BOS. |
Clinicogenomic associations in childhood Langerhans cell histiocytosis: an international cohort study. Thus, the correlation of BRAFV600E with inferior clinical outcome is (primarily) driven by its association with disease extents known for high rates of progression or relapse, including multisystem LCH. These findings advance our understanding of factors underlying the remarkable clinical heterogeneity of LCH, but also question the independent prognostic value of lesional BRAFV600E status. |
Eltrombopag in patients with chronic immune thrombocytopenia in Asia-Pacific, Middle East, and Turkey: final analysis of CITE. Adverse events occurred in 50.9% of patients (n=116), the most common being upper respiratory tract infection (8.3%) and headache (6.6%). These findings confirmed effectiveness of eltrombopag treatment in routine practice and reassured that real-world compliance to eltrombopag prescribed doses and dietary instructions in the Asia-Pacific, Middle East, and Turkey were in line with current recommendations. |
Mast Cell Leukemia: Clinical and Molecular Features and Survival Outcomes of Patients in the ECNM Registry. In multivariate analysis (S/A/R mutations excluded due to low event rates), a diagnosis of MCL-AHN (HR 4.7, 95% CI 1.7 - 13.0, p = 0.001) and abnormal karyotype (HR 5.6, 95% CI 1.4 - 13.3, p = 0.02) were associated with inferior OS; KIT D816V positivity (HR 0.33, 95% CI 0.11 - 0.98, p = 0.04) and midostaurin treatment (HR 0.32, 95% CI 0.08 - 0.72, p = 0.008) were associated with superior OS. These data provide the most comprehensive snapshot of the clinicopathologic, molecular, and treatment landscape of MCL to date, and should help further inform subtyping and prognostication of MCL. |
NADPH oxidase 2 limits amplification of IL-1ß-G-CSF axis and an immature neutrophil subset in murine lung inflammation. Thus, neutrophil-produced IL-1ß and downstream G-CSF act sequentially but non-redundantly with LTB4 to deploy neutrophils and amplify inflammation in CGD mice following inhalation of zymosan. NOX2 plays a critical role in dampening multiple components of a feed-forward pipeline for neutrophil recruitment, and these findings highlight NOX2 as a key regulator of neutrophil number, subsets and function at inflamed sites. |
Peri-CAR-T practice patterns and survival predictors for all CAR-T patients and post-CAR-T failure in aggressive B-NHL. AlloHCT for select patients at any time following CAR-T failure (n=16) led to durable responses in over half at one-year. These data provide a benchmark for future clinical trials in patients with progression post-CAR-T, an unmet clinical need. |
Proinflammatory microenvironment promotes lymphoma progression in mice with high megakaryocyte and TPO levels. Moreover, RNA sequencing of blood-resident Eµ-myclymphoma cells from TpoTgand wild-type mice after tumour transplant revealed upregulation of hallmark gene sets associated with inflammatory response in TpoTg mice. We propose that a pro-inflammatory microenvironment in TpoTgmice promoted lymphoma progression. |
Prospective hemophilia inhibitor PUP study reveals distinct antibody signatures during FVIII inhibitor eradication. Interestingly, one patient with partial ITI success and one patient with ITI failure developed apparent oligoreactive FVIII-binding antibodies during ITI. The explanation of the true nature of these antibodies requires more comprehensive follow-ups in future studies. |
Sequential Pembrolizumab and AVD is Highly Effective at any PD-L1 Expression Level in Untreated Hodgkin Lymphoma. The high response rates observed at al PD-ligand levels suggest that even low levels of PD ligand expression are sufficient for response to PD-1 blockade in untreated cHL. An international phase II trial (NCT05008224) to confirm these findings is ongoing. |
Sickle cell disease is a risk factor for transplant-associated thrombotic microangiopathy in children. In available pre-HCT samples, there were no differences in complement biomarkers in those with SCD and those without, though SCD patients did have significantly higher markers of endothelial activation, sVCAM-1 and p-selectin levels. In conclusion, children with SCD merit careful screening for TA-TMA post HCT, particularly those receiving a haploidentical HCT. |
The outcome of older adults with classic Hodgkin lymphoma in British Columbia. With a median follow-up of 9 years, 5-year disease specific (DSS) and overall survival (OS) have improved by decade comparison (both p 70 even in the mod-ern treatment era. Further, treatment-related toxicity remains a significant concern and use of bleo-mycin should be avoided in most patients. |
| Blood Cancer J |
Defining new reference intervals for serum free light chains in individuals with chronic kidney disease: Results of the iStopMM study. The crude prevalence of LC-MGUS in CKD patients was 0.5%. We conclude that current reference intervals for FLC and FLC ratio are inaccurate in CKD patients and propose new eGFR based reference intervals to be implemented. |
| Haematologica |
Activation of lncRNA NEAT1 leads to survival advantage of multiple myeloma cells by supporting a positive regulatory loop with DNA repair proteins. Overall, we provided novel important insights into NEAT1 role in supporting MM cells adaptation to stressful conditions by improving the maintenance of DNA integrity. Taken together, our results suggest that NEAT1, and probably PS organelles, could represent a potential therapeutic target for MM treatment. |
Targeting dual oncogenic machineries driven by TAL1 and PI3K-AKT pathways in Tcell acute lymphoblastic leukemia. TAL1-positive, AKT-activated T-ALL cells were very sensitive to PIK-75, as evidenced by the growth inhibition and apoptosis induction, while T-ALL cells that exhibited activation of the JAK-STAT pathway were insensitive to this drug. Together, our study demonstrates a strategy targeting two types of core machineries mediated by oncogenic transcription factors and signaling pathways in T-ALL. |
| J Hematol Oncol |
Elraglusib (9-ING-41), a selective small-molecule inhibitor of glycogen synthase kinase-3 beta, reduces expression of immune checkpoint molecules PD-1, TIGIT and LAG-3 and enhances CD8+ T cell cytolytic killing of melanoma cells. These data highlight the potential of elraglusib as an immune-modulatory agent and demonstrate the benefit of a sequential approach with immune checkpoint inhibition followed by GSK-3ß inhibition in melanoma and provide a rationale for clinical investigation of elraglusib combined with immune checkpoint inhibitory molecules, including those targeting PD-1, TIGIT and LAG-3. This has several potential implications for current immunotherapy regimes, including possibly reducing the intensity of anti-PD-1 mAb treatment needed for response in patients receiving elraglusib, especially given the benign adverse event profile of elraglusib observed to date. Based on these data, a clinical study of elraglusib, an anti-PD-1 mAb and chemotherapy is ongoing (NCT NCT05239182). |
| Lancet Haematol |
Postnatal treatment for children with fetal and neonatal alloimmune thrombocytopenia: a multicentre, retrospective, cohort study. Our data suggest that HPA-matched transfusions lead to a larger median platelet count increment than HPA-unmatched transfusions, but whether HPA matching is also associated with a reduced risk of bleeding remains unknown. Funding Sanquin. |
Tisagenlecleucel therapy for relapsed or refractory B-cell acute lymphoblastic leukaemia in infants and children younger than 3 years of age at screening: an international, multicentre, retrospective cohort study. Interpretation These data suggest that tisagenlecleucel has antitumour activity and has an acceptable safety profile for young children and infants with B-cell precursor acute lymphoblastic leukaemia. Funding None. |
| Leukemia |
Incidence of subsequent malignancies after total body irradiation-based allogeneic HSCT in children with ALL - long-term follow-up from the prospective ALL-SCT 2003 trial. This analysis confirms and quantifies the increased risk of SMN in children with ALL after conditioning with TBI. Future strategies to avoid TBI will need careful tailoring within prospective, controlled studies to prevent unfavorable outcomes. |
Pregnancy and childbirth outcomes in women with myeloproliferative neoplasms-a nationwide population-based study of 342 pregnancies in Sweden. Incidence was 12.2 per 100.000 pregnancies. In summary, preterm birth was an important complication in MPN pregnancies, while maternal complications were less common than previously reported. |
Prospective validation of a biomarker-driven response prediction model to romiplostim in lower-risk myelodysplastic neoplasms - results of the EUROPE trial by EMSCO. Sequential analysis of variant allelic frequency of mutations like SRSF2 did not reveal an impact of ROM on clonal evolution in both responders and non-responders. In summary, our study confirms the safety and efficacy of ROM in LR-MDS patients and may allow to better define subgroups of patients with a high likelihood of response. |
| Thromb Haemost |
Hemostatic Effects of Tranexamic Acid in Cesarean Delivery: An Ancillary Study of the TRAAP2 Study. GFC/LT evidenced fibrinolysis activation during cesarean delivery, linked to a decrease in fibrinolytic inhibitors. GFC/LT revealed a significant antifibrinolytic effect of TXA compared with placebo. |
Parenteral Antiplatelet Drugs in ST-Elevation Myocardial Infarction: Current Status and Future Directions. Novel parenteral antiplatelet drugs, such as cangrelor, selatogrel, and zalunfiban, have been recently developed to achieve rapid, potent antiplatelet effects while preserving hemostasis. We provide a description of currently available parenteral antiplatelet agents and of those in clinical development for prehospital administration in STEMI patients. |
Protein Tyrosine Phosphatase 1B Deficiency in Vascular Smooth Muscle Cells Promotes Perivascular Fibrosis following Arterial Injury. Chronic reduction of PTP1B in SMCs promotes dedifferentiation, perivascular fibrosis, and adverse remodeling following vascular injury by mechanisms involving an ERK1/2 phosphorylation-driven shift from SMAD2 to KLF4-regulated gene transcription. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Am J Hematol |
| Ann Oncol |
| Blood |
| J Hematol Oncol |
Enhancing the therapeutic efficacy of nanoparticles for cancer treatment using versatile targeted strategies. Additionally, stimuli-responsive nanoplatforms have also been considered as a promising and effective targeting strategy against tumors, as these nanoplatforms maintain their stealth feature under normal conditions, but upon homing in on cancerous lesions or their microenvironment, are responsive and release their cargoes. In this review, we comprehensively summarize the field of active targeting drug delivery systems and a number of stimuli-responsive release studies in the context of emerging nanoplatform development, and also discuss how this knowledge can contribute to further improvements in clinical practice. |
Liquid biopsy: current technology and clinical applications. In conclusion, liquid biopsy is a powerful tool, and remarkable advances in this technology have impacted multiple aspects of precision oncology, from early diagnosis to management of refractory metastatic disease. Future research may focus on fluids beyond blood, such as ascites, effusions, urine, and cerebrospinal fluid, as well as methylation patterns and elements such as exosomes. |
Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets. g., 3,10-dibromofascaplysin combined with olaparib) to exhibit therapeutic potential against various cancers by regulating RCD subroutines. In short, the information provided in this review on the regulation of cell death by indole alkaloids against different targets is expected to be beneficial for the design of novel molecules with greater targeting and biological properties, thereby facilitating the development of new strategies for cancer therapy. |
The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis. In this review, we described the molecular mechanisms, signaling pathways, and the stages of tumorigenesis involved in the EMT process and discussed the dynamic non-binary process of EMT and its role in tumor metastasis. Finally, we summarized the challenges of chemotherapy and immunotherapy in EMT and proposed strategies for tumor therapy targeting EMT. |
misc publications eg case reports, tools of the trade, images of the month, etc…
| Blood |
| Blood Adv |
| Lancet Haematol |
| Leukemia |
Letters to the editors and authors’ replies
| Am J Hematol |
Haploidentical transplantation with post-transplant cyclophosphamide versus single cord blood transplantation for myelodysplastic syndrome: a retrospective study from the Adult Myelodysplastic Syndrome Working Group of the Japanese Society for Transplantation and Cellular Therapy (JSTCT). |
| Blood Cancer J |